It has been suggested that neuropeptide Y (NPY) and corticotropin releasing factor (CRF) exert a reciprocal regulation on ethanol self-administration via allostatic interactions within the extended amygdala. Repeated abstinence and relapse may alter the balance between NPY and CRF, promoting uncontrolled ethanol intake. The alcohol deprivation effect (ADE), characterized by robust increases of ethanol drinking following a period of ethanol abstinence, has been proposed to be an animal model of uncontrolled ethanol drinking. Here we test the hypothesis that low NPY signaling, and increased CRF signaling, contributes to the uncontrolled ethanol drinking associated with the ADE. Specifically, we will determine if administration of exogenous NPY will protect against the acquisition and/or expression of the ADE (Specific Aim 1), if mutant mice lacking NPY are more susceptible to the ADE (Specific Aim 2), and if administration of a CRF antagonist protects against the acquisition and/or expression of the ADE (Specific Aim 3). Thus, the proposed experiments employ both genetic and pharmacological techniques in order to determine the role of NPY and CRF signaling system on uncontrolled ethanol self-administration stemming from the ADE.